Polysialic acid-based nanoparticles for enhanced targeting and controlled dexamethasone release in pulmonary inflammation treatment

Cong Li; Jing Li; Yujie Bai; Kexin Zhang; Zeyu Wang; Yifan Zhang; Qingyu Guan; Shiqi Wang; Zehao Li; Zhihang Li; Lijiang Chen

doi:10.1016/j.ijbiomac.2025.139550

Polysialic acid-based nanoparticles for enhanced targeting and controlled dexamethasone release in pulmonary inflammation treatment

Int J Biol Macromol. 2025 Jan 6:139550. doi: 10.1016/j.ijbiomac.2025.139550. Online ahead of print.

Authors

Cong Li¹, Jing Li², Yujie Bai², Kexin Zhang², Zeyu Wang², Yifan Zhang², Qingyu Guan², Shiqi Wang², Zehao Li², Zhihang Li², Lijiang Chen³

Affiliations

¹ School of Pharmaceutical Science, Liaoning University, Shenyang 110036, China; Liaoning Key Laboratory for New Drug Development, Shenyang 110036, China.
² School of Pharmaceutical Science, Liaoning University, Shenyang 110036, China.
³ School of Pharmaceutical Science, Liaoning University, Shenyang 110036, China; Liaoning Key Laboratory for New Drug Development, Shenyang 110036, China. Electronic address: clj1172023@163.com.

PMID: 39778853
DOI: 10.1016/j.ijbiomac.2025.139550

Abstract

Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are life-threatening conditions characterized by severe inflammation and respiratory failure. Despite the use of dexamethasone (Dex) in treatment, challenges such as poor solubility and systemic side effects persist, highlighting the need for novel therapeutic approaches. This study introduces an innovative nanoparticle delivery system based on chitosan (CS) and polysialic acid (PSA), engineered via electrostatic assembly, to improve the targeted delivery of Dex to inflamed lung tissues. To enhance drug encapsulation and stability, novel taurine-Vitamin E succinate amphiphilic molecules (TVES and TGVES) were synthesized. The unique ability of PSA to specifically target Siglec-1 receptors on M1 macrophages-key contributors to ALI/ARDS-related inflammation-positions this system as a promising strategy for targeted pulmonary therapies. In vitro targeting of M1 macrophages and in vivo reduction of inflammation demonstrate the potential to transform treatment by delivering therapeutic agents precisely to the site of need. This cutting-edge nanoparticle platform not only holds promise for improving ALI/ARDS outcomes but also paves the way for the application of functional additives like taurine in advanced medical therapies.

Keywords: Polysialic acid-chitosan polyelectrolyte complexes; Targeting lung inflammation; Taurine-vitamin E succinate Amphiphiles.